Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects.

IF 5.9 2区 医学 Q2 CELL BIOLOGY
Neural Regeneration Research Pub Date : 2026-04-01 Epub Date: 2025-06-19 DOI:10.4103/NRR.NRR-D-24-01371
Zijun Wu, Yuying Zhao, Shujing Hao, Mengyao An, Chengcheng Song, Jing Li
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引用次数: 0

Abstract

Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism. Previous studies have shown that PPARα plays a key role in the onset and progression of neurodegenerative diseases. Consequently, peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders. This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases. Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues. Although it is conventionally believed to be primarily localized in the nucleus, its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling. Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects. Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases. For instance, peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway. Additionally, peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra, and it can mitigate motor dysfunction in Parkinson's disease mouse models. Furthermore, peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases. In summary, peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases, and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases, providing new options for patient care.

过氧化物酶体增殖物激活受体在神经退行性疾病和其他神经系统疾病中的作用:临床应用前景。
摘要:过氧化物酶体增殖体激活受体α是核激素受体超家族的成员,是参与调节细胞代谢的转录因子。先前的研究表明,PPARα在神经退行性疾病的发生和发展中起着关键作用。因此,过氧化物酶体增殖体激活受体α激动剂作为神经系统疾病的潜在治疗方法已引起越来越多的关注。现就过氧化物酶体增殖物激活受体在神经系统疾病中的研究进展作一综述。过氧化物酶体增殖体激活受体存在于成年小鼠和成年神经组织的所有细胞类型中。虽然传统上认为它主要定位于细胞核,但它的功能可能受到细胞质和核穿梭之间的动态平衡的调节。内源性和外源性过氧化物酶体增殖物激活受体α激动剂都与过氧化物酶体增殖物激活反应元件结合,发挥其生物学作用。过氧化物酶体增殖物激活受体在神经退行性疾病中起着重要的治疗作用。例如,过氧化物酶体增殖体激活受体激动剂gemfibrozil已被证明通过自噬-溶酶体途径降低阿尔茨海默病小鼠模型海马中可溶性和不可溶性淀粉样蛋白- β的水平。此外,过氧化物酶体增殖物激活受体α对于黑质的正常发育和功能维持至关重要,它可以减轻帕金森病小鼠模型的运动功能障碍。此外,已发现过氧化物酶体增殖物激活受体α可减少各种神经系统疾病的神经炎症和氧化应激。综上所述,过氧化物酶体增殖物激活受体α在多种神经系统疾病的发生和发展中起着至关重要的作用,过氧化物酶体增殖物激活受体α激动剂有望成为治疗神经退行性疾病的新药物,为患者护理提供新的选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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